Arteriosclerosis which, inter alia, is attributable to cholesterol deposits in the arterial vascular walls is one of the most frequent causes of death in the industrialised nations of the West. Depending on where the deposits occur, impairment of blood circulation in the brain (stroke), impairment of blood circulation in the heart (coronary heart disease, myocardial infarction) and arterial occlusive diseases in the peripheral arteries may occur. Investigations have shown that the risk of suffering from arteriosclerosis corresponds to the proportion of cholesterol present in the blood. This cholesterol is present in the form of lipoprotein particles which contain cholesterol, for example, together with proteins. These lipoproteins effect the transport of the water-insoluble lipids in the blood. Lipoproteins can be subdivided into different lipoprotein classes, inter alia, on the basis of their density, lipid components and apolipoproteins. The risk of suffering from arteriosclerosis appears to correlate to a high level of LDL (low density lipoprotein) cholesterol. In contrast, cholesterol in HDL particles (high density lipoprotein) seems to contribute to the removal of arteriosclerotic plaques in arterial vascular walls. Further investigations indicate that certain size and density distributions within lipoprotein classes are a good indicator for the early recognition of cardiovascular diseases and the risk of suffering of arteriosclerosis (Kuller et al., (2002), Nuclear Magnetic Resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study, Aterioscler. Thromb. Vasc. Biol. 22, 1175-1180; Blake et al., (2002), Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women, Circulation 106, 1930-1937; Rosenson et al., (2002), Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the pravastatin limitation of arteriosclerosis in the coronary arteries (PLAC-I Trial), Am. J. Cardiol. 90, 89-94; Rosenson et al., (2002), Effects of pravastatin treatment on lipoprotein subclass profiles and particle size in the PLAC-I trial, arteriosclerosis 160, 41-48). For this reason, numerous lipoprotein determinations in the blood are carried out for the early recognition of cardiovascular diseases. It is assumed that the object of up to 60-80% of the diagnostic blood tests in the laboratory is, at least partially, the determination of lipoprotein.
From EP 0 361 214 B1, a process for the determination of the concentration of four lipoproteins in a blood plasma sample by NMR measurements is known. In this process, the line contour of an NMR spectrum of a plasma sample to be analysed is fitted by a weighted linear combination of the four lipoprotein reference spectra. By refining the weighting coefficients of the individual reference spectra, the concentrations of the four lipoprotein components can be calculated. In the case of this process, however, no size distributions and density distributions can be determined within one lipoprotein class.
In the review article “Nuclear magnetic resonance chromatography: applications of pulse field gradient diffusion NMR to mixture analysis and ligand-receptor interaction”, Journal of chromatography B; 725 (1999), pages 79-90, a complicated process for investigating protein-ligand interactions is disclosed in the case of which proteins specifically 13C/15N-labelled for NMR spectroscopy are used, apart from pulse field gradient NMR.